| Project/Area Number |
18591015
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Endocrinology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAWARA Akira Tohoku University, TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, PROFESSOR (90270834)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Sadayoshi TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, 大学院・医学系研究科, PROFESSOR (40271613)
SATO Yasufumi TOHOKU UNIVERSITY INSTITUTE OF DEVELOPMENT, AGING AND CANCER, PROFESSOR (50178779)
KAGECHIKA Hiroyuki TOKYO MEDICAL AND DENTAL UNIVERSITY, SCHOOL OF BIOMEDICAL SCIENCE, PROFESSOR (20177348)
SATO Akira TOHOKU UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, LECTURER (20250764)
宇留野 晃 東北大学, 病院・医員 (90396474)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,790,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | all-trans retinoic acid / retinoic acid receptor / angiogenesis / retinoid / endothelial cells / all-trans retinoic acid / retinoic acid receptor / angiogenesis / retinoid / endothelial cells / 血管内皮増殖因子 / 動脈硬化 / 受容体 |
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| Research Abstract |
A natural retinoid all-trans retinoic acid (ATRA) regulates a variety of important cellular functions via retinoic acid receptor (RAR). ATRA has therapeutically been utilized against various malignancies including acute promyelocytic leukemia. Recently, ATRA has also been recognized to be beneficial against atherosclerotic vascular disorders. However, its effects on angiogenesis remain controversial. We therefore examined ATRA effects on in vitro angiogenesis in terms of capillary-like tube formation using human umbilical vein endothelial cells (HUVEC)/normal human dermal fibroblasts (NHDF) co-culture. ATRA as well as RAR agonist Am80 significantly induced capillary-like tube formation. The ATRA-induced tube formation was inhibited by co-incubation with RAR antagonist LE540/LE135. HUVEC proliferation, but not its migration, was also induced by ATRA. The ATRA-induced tube formation was completely abolished by co-incubation with vascular endothelial growth factor (VEGF) neutralizing antibody or with VEGF receptor (VEGFR)-2 (KDR) neutralizing antibody, but not with VEGFR-1 (Flt-1) neutralizing antibody. ATRA and Am80 induced VEGF gene promoter in NHDF was stimulated by ATRA, which was augmented by RAR overexpression. ATRA also induced VDGFR-2/KDR mRNA expression in HUVEC. Moreover, ATRA induced secretion of hepatocyte growth factor (HGF) as well as angiopoietin-2 (Ang-2) in the co-culture. Taken together, ATRA may have induced angiogenesis via RAR mainly by stimulation of HUVEC proliferation and enhancement of endogenous VEGF signaling, and in part by induction of HGF and Ang-2 production. Retinoids may therefore be potential candiadates for therapeutic angiogenesis against ischemic vascular disorders.
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